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This work presents an in-depth experimental study aimed at assessing the impact of natural weathering on the behavior of high-density polyethylene (HDPE) bottles. To this end, several analytical techniques were employed, including Fourier transform infrared spectroscopy (FTIR) to examine molecular changes, scanning electron microscopy (SEM) to study morphology, thermogravimetric analysis (TGA) to assess thermal properties, and tensile and compression tests to evaluate mechanical properties. The results obtained reveal significant changes in HDPE exposed to natural weathering. FTIR analysis enabled us to identify that the 1IDPE bottles had been subjected to an oxidation process initiated b) the absorption of solar radiation during natural weathering treatments, while SEM analysis showed the presence of holes resulting from the detachment of material fragments after exposure, TGA analysis confirms the impact of natural exposure time on the decrease in the average molecular weight and chemical degradation of HDPE macromolecules, through a reduction in the initial degradation temperature and the maximum thermodegradation temperature. However, tensile and compressive tests showed a reduction in the mechanical strength of HDPE after exposure to natural conditions, with notable variations depending on environmental conditions, making the material damaged. These results enabled us to calculate the damage caused by three damage laws. These results offer important insights into the mechanisms of HDPE degradation under the influence of natural climatic factors, paving the way for the development of more resistant and durable packaging materials in the face of variable environmental conditions. Highlights * The objective of this study is to analyze and describe the effects of natural weathering on high-density polyethylene bottles. This involves evaluating the deterioration of physicochemical, mechanical, and morphological properties. Additionally, three damage laws aBe employed to assess the extent of damage inflicted by this material. * Analytical techniques were used, including SEM, FT1R, and TGA, tensile and compressive test. KEYWORDS damage, FTIR, HDPE bottles, natural weathering, SEM, TGA, 1 | INTRODUCTION Growing demand in sectors such as packaging, automotive and construction has led to an exponential increase in global plastics consumption since the 1950s. (1,2) Packaging plays an [...]

The primary aim of the current investigation is to contribute to SARS-CoV-2 research by identifying potential lead compounds for clinical applications, with a specific focus on inhibitors targeting the main protease (Mpro). In this research, molecular docking analysis was conducted using the software molecular operating environmental (MOE) to evaluate the potency of bioactive compounds sourced from medicinal plants as inhibitors of SARS- -CoV-2 Mpro. Among 118 natural compounds with anti-HIV characteristics, the top seven candidates (h3, h84, h85, h87, h90, h108 and h110), were identified based on their superior binding energies with comparison to the reference ligand N3. These selected compounds exhibited binding affinities of –33.996, –35.336, –32.615, –32.154, –33.452, –31.903 and –40.360 kJ mol-1, respectively. To further refine our shortlist of potential candidates for human application, we examined the drug-likeness, and the pharmaceutical attributes of these compounds using the SwissADME web server. Among them, only two compounds, namely h85 and h87, demonstrated favorable pharmacological properties suitable for human administration. These two compounds were subsequently shortlisted for further investigation. To explore the conformational stability of ligands within the Mpro active site, we performed molecular dynamics (MD) simulations. These simulations showed reliable and steady trajectories, supported by analyses of root-mean-square-fluctuation (RMSF) and root- -mean-square deviation (RMSD). These findings and favorable molecular properties as well as interaction profiles suggest that these two lead compounds may be promising SARS-CoV-2 therapeutic candidates. They present exciting starting points for further drug design.

Background: The increasing prevalence of diabetes and the side effects associated with current medications necessitate the development of novel candidate drugs targeting alpha-glucosidase as a potential treatment option. Methods: This study employed computer-aided drug design techniques to identify potential alpha-glucosidase inhibitors from the PubChem database. Molecular docking was used to evaluate 81,197 compounds, narrowing the set for further analysis and providing insights into ligand-target interactions. An ADMET study assessed the pharmacokinetic properties of these compounds, including absorption, distribution, metabolism, excretion, and toxicity. Molecular dynamics simulations validated the docking results. Results: 9 compounds were identified as potential candidate drugs based on their ability to form stable complexes with alpha-glucosidase and their favorable pharmacokinetic profiles, three of these compounds were subjected to the molecular dynamics, which showed stability throughout the entire 100 ns simulation. Conclusion: These findings suggest promising new alpha-glucosidase inhibitors for diabetes treatment. Further validation through in vitro and in vivo studies is recommended to confirm their efficacy and safety. [ABSTRACT FROM AUTHOR]

Hemisynthesis makes it possible to improve the activity or reduce the toxicity of a biocompound by modifying or adding peripheral groups. Catechin present in different plant species was known for its moderate anti-malarial and anti-SARS-CoV-2 activities. The aim of this work was focused on the identification of new compounds with potential anti-SARS-CoV-2 and/or anti-malarial activities, evaluated through In silico simulation. A polyphenol pharmacophore model, based on (+)-catechin (1) was virtually constructed using previously reported inhibitors. N- and/or S-heterocyclic fragments were inserted on the backbone of (+)-catechin and 12 pharmacophore hypotheses were studied. This study targeted 3 proteins biologically responsible for SARS-CoV-2 (PDB ID: 7JYC, 6M0J, and 6HZD) and one protein responsible for malaria (PDB ID: 3SRJ). Molecular docking had shown that the new catechin-aldehyde candidates have good Ligand-Protein affinity in terms of free energy compared to the study reference Narlaprevir and Artesunate for SARS-CoV-2 and malaria respectively. Theoretically, most compounds didn't show toxicity except compounds 2a, 2i, and 2k, exhibiting hepatotoxic activity. Molecular dynamics was used to prove and assess their binding stability to the target protein for each activity. The 3SRJ-2f and 6HZD-2l structures were selected for anti-malarial and anti-SARS-CoV-2 activity respectively. The 3SRJ-2f and 6HZD-2l complexes showed stable interactions to 100 ns between the inhibitor fragments and the residual amino acids of the protein. To conclude, these novel compounds are probably to become promising lead molecules for the development of effective anti-SARS-CoV-2 and/or anti-malarial of all drugs. [ABSTRACT FROM AUTHOR]

Candida albicans and Aspergillus fumigatus are recognized as significant fungal pathogens, responsible for various human infections. The rapid emergence of drug-resistant strains among these fungi requires the identification and development of innovative antifungal therapies. We undertook a comprehensive screening of 297 naturally occurring compounds to address this challenge. Using computational docking techniques, we systematically analyzed the binding affinity of each compound to key proteins from Candida albicans (PDB ID: 1EAG) and Aspergillus fumigatus (PDB ID: 3DJE). This rigorous in silico examination aimed to unveil compounds that could potentially inhibit the activity of these fungal infections. This was followed by an ADMET analysis of the top-ranked compound, providing valuable insights into the pharmacokinetic properties and potential toxicological profiles. To further validate our findings, the molecular reactivity and stability were computed using the DFT calculation and molecular dynamics simulation, providing a deeper understanding of the stability and behavior of the top-ranking compounds in a biological environment. The outcomes of our study identified a subset of natural compounds that, based on our analysis, demonstrate notable potential as antifungal candidates. With further experimental validation, these compounds could pave the way for new therapeutic strategies against drug-resistant fungal pathogens. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase (AChE) is one of the main drug targets for treating Alzheimer's disease. This current study relies on multiple molecular modeling approaches to develop new potent inhibitors of AChE. We explored a 2D QSAR study using the statistical method of multiple linear regression based on a set of substituted 5-phenyl-1,3,4-oxadiazole and N-benzylpiperidine analogs, which were recently synthesized and proved their inhibitory activities against acetylcholinesterase (AChE). The molecular descriptors, polar surface area, dipole moment, and molecular weight are the key structural properties governing AChE inhibition activity. The MLR model was selected based on its statistical parameters: R2 = 0.701, R2test = 0.76, Q2CV = 0.638, and RMSE = 0.336, demonstrating its predictive reliability. Randomization tests, VIF tests, and applicability domain tests were adopted to verify the model's robustness. As a result, 11 new molecules were designed with higher anti-Alzheimer's activities than the model molecule. We demonstrated their improved pharmacokinetic properties through an in silico ADMET study. A molecular docking study was conducted to explore their AChE inhibition mechanisms and binding affinities in the active site. The binding scores of compounds M1, M2, and M6 were (−12.6 kcal/mol), (−13 kcal/mol), and (−12.4 kcal/mol), respectively, which are higher than the standard inhibitor Donepezil with a binding score of (−10.8 kcal/mol). Molecular dynamics simulations over 100 ns were used to validate the molecular docking results, indicating that compounds M1 and M2 remain stable in the active site, confirming their potential as promising anti-AChE inhibitors. [ABSTRACT FROM AUTHOR]

A set of 5-(substituted benzylidene) thiazolidine-2,4-dione derivatives was explored to study the main structural requirement for the design of protein tyrosine phosphatase 1B (PTP1B) inhibitors. Utilizing multiple linear regression (MLR) analysis, we constructed a robust quantitative structure–activity relationship (QSAR) model to predict inhibitory activity, resulting in a noteworthy correlation coefficient (R2) of 0.942. Rigorous cross-validation using the leave-one-out (LOO) technique and statistical parameter calculations affirmed the model's reliability, with the QSAR analysis revealing 10 distinct structural patterns influencing PTP1B inhibitory activity. Compound 7e(ref) emerged as the optimal scaffold for drug design. Seven new PTP1B inhibitors were designed based on the QSAR model, followed by molecular docking studies to predict interactions and identify structural features. Pharmacokinetics properties were assessed through drug-likeness and ADMET studies. After that density functional theory (DFT) was conducted to assess the stability and reactivity of potential diabetes mellitus drug candidates. The subsequent dynamic simulation phase provided additional insights into stability and interactions dynamics of the top-ranked compound 11c. This comprehensive approach enhances our understanding of potential drug candidates for treating diabetes mellitus. [ABSTRACT FROM AUTHOR]

In this investigation, we undertook a comprehensive quantitative structure-activity relationship (QSAR) analysis using both modern artificial neural network (ANN) methods and classical multiple linear regression methods (MLR). Our primary focus was on revealing the intricate connection between antidiabetic activity and the molecular structure of thirty-nine imidazolidine-2,4-dione derivatives. The B3LYP hybrid functional and 6-31G (d) basis set computed electronic properties at the quantum level. Rigorous benchmarking against experimental data validated the reliability of our quantum theory approach. Our statistical model effectively predicted activities closely aligned with experimental antidiabetic activities, quantified by the IC50 values. They also revealed a significant superiority of the ANN architecture (6-4-1) over the MLR method. This study stands as a meaningful contribution to the field, providing valuable insights for designing new antidiabetic drugs, particularly as potential inhibitors of tyrosine phosphate 1B (PTP1B). The explicit articulation of our primary aim and emphasis on the study's significance underscore its potential impact on advancing drug development within the realm of antidiabetic therapeutics. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to explore the potential of natural anticoagulant compounds as synergistic inhibitors of the main protease (Mpro) and papain-like protease (PLpro) of SARS-CoV-2 and find effective therapies against SARS-CoV-2 by investigating the inhibitory effects of natural anticoagulant compounds on key viral proteases., Objective: The objectives of this study were to conduct rigorous virtual screening and molecular docking analyses to evaluate the binding affinities and interactions of selected anticoagulant compounds with Mpro and PLpro, to assess the pharmacokinetic and pharmacodynamic profiles of the compounds to determine their viability for therapeutic use, and to employ molecular dynamics simulations to understand the stability of the identified compounds over time., Methods: In this study, a curated collection of natural anticoagulant compounds was conducted. Virtual screening and molecular docking analyses were performed to assess binding affinities and interactions with Mpro and PLpro. Furthermore, pharmacokinetic and pharmacodynamic analyses were carried out to evaluate absorption, distribution, metabolism, and excretion profiles. Molecular dynamics simulations were performed to elucidate compound stability., Results: Natural compounds exhibiting significant inhibitory activity against Mpro and PLpro were identified. A dual-target approach was established as a promising strategy for attenuating viral replication and addressing coagulopathic complications associated with SARS-CoV-2 infection., Conclusion: The study lays a solid foundation for experimental validation and optimization of identified compounds, potentially leading to the development of precise treatments for SARS-CoV-2., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Aspergillus fumigatus, a significant fungal pathogen, poses a threat to human health, especially in immunocompromised individuals. Addressing the need for novel antifungal strategies, this study employs virtual screening to identify potential inhibitors of Fructosamine oxidase, also known as Amadoriase II, a crucial enzyme in A. fumigatus (PDB ID: 3DJE)., Method: Virtual screening of 81,197 triazole derivatives was subjected to computational analysis, aiming to pinpoint molecules with high binding affinity to the active site of Fructosamine oxidase. Subsequently, an in-depth ADMET analysis assessed the pharmacokinetic properties of lead compounds, ensuring their viability for further development. Molecular dynamics simulations were performed to evaluate the stability of top-ranked compounds over time., Results: The results unveil a subset of triazole derivatives displaying promising interactions, suggesting their potential as inhibitors for further investigation., Conclusion: This approach contributes to the development of targeted antifungal agents, offering a rational starting point for experimental validation and drug development against Aspergillus fumigatus infections., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The rising prevalence of diabetes necessitates the development of novel drugs, especially given the side effects associated with current medications like Acarbose and Voglibose. A series of 36 Hydrazinyl thiazole-linked indenoquinoxaline derivatives with notable activity against alpha-amylase were studied. To create a molecular model predicting alpha-amylase activity, a QSAR study was performed on these compounds. Molecular descriptors were calculated using Chem3D and Gaussian software and then correlated with their IC 50 biological activities to form a dataset. This model data was refined using PCA and modeled with MLR. The model's performance was statistically verified ( R 2 =0.800; R adj 2 = 0.767; R cv 2 = 0.651) and its applicability domain was defined. It was predicted to possess high predictive power ( R test 2   = 0.872). Based on this, new compounds were proposed, and their activities were predicted using the developed model. Additionally, their binding ability to the biological target was studied through molecular docking and dynamics. Their pharmacokinetics were also evaluated using ADMET predictions. Two designed compounds named AE and AB emerged as particularly promising, displaying properties that suggest substantial therapeutic potential and they can form stable complexes into the binding pocket of alpha-amylase enzyme.Communicated by Ramaswamy H. Sarma.